Safety of etanercept in psoriasis: a critical review.

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients' treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro. The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis. There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events. In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women. Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.

[Prognostic factors of localized malignant melanoma: study of 639 patients]. / Factores pronósticos en el melanoma maligno cutáneo localizado: estudio de 639 pacientes.

BACKGROUND AND OBJECTIVE: Several clinical and histological prognostic factors have been identified in localized melanoma. However, further studies with better defined and more reproducible histological parameters are needed. Our aim was to identify the prognostic factors for survival in cutaneous melanoma in the Spanish population. PATIENTS AND METHOD: Six hundred and thirty nine patients with localized melanoma, stages I and II of the last version of the American Joint Committee on Cancer staging system for cutaneous melanoma, with 2 years of follow-up or documented relapse, were selected from the database of the Department of Dermatology. Univariate and multivariate Cox regression analyses were performed for overall and disease free survival. RESULTS: Tumor thickness appeared as the most important prognostic factor for both overall and disease free survival in the multivariate analysis. Inflammatory infiltrate and sex were only significant for overall survival, and location, age and ulceration were significant for disease free survival. Other variables, such as histological type, mitotic rate or level of invasion, lost their prognostic significance in the multivariate analysis. CONCLUSIONS: Tumor thickness is the most important prognostic factor to predict survival in localized melanoma. Other factors such as sex, inflammatory infiltrate, location, age or ulceration, have also an important role in prognosis.

Factores pronósticos en el melanoma maligno cutáneo localizado: estudio de 639 pacientes / Prognostic factors of localized malignant melanoma: study of 639 patients

FUNDAMENTO Y OBJETIVO: Se han identificado múltiples factores pronósticos, tanto clínicos como histológicos, en los pacientes con melanoma localizado. Sin embargo, hacen falta nuevos estudios con definiciones más claras y reproducibles de las variables histológicas. El objetivo de este estudio es identificar factores pronósticos para la supervivencia de pacientes con melanoma cutáneo en una muestra de la población española. PACIENTES Y MÉTODO: Se seleccionó a 639 pacientes con melanoma cutáneo localizado, estadios Iy II de la última versión del sistema de estadificación del American Joint Committee on Cancer, con un mínimo período de seguimiento de 2 años o recaída bien documentada, de la base de datos del Servicio de Dermatología del hospital. Se hizo un estudio de la supervivencia global y de la supervivencia libre de enfermedad mediante los métodos de Kaplan-Meier y Cox. RESULTADOS: El espesor tumoral fue el factor pronóstico más importante tanto para la supervivencia global como para la supervivencia libre de enfermedad tras el estudio multivariado. El infiltrado inflamatorio y el sexo lo fueron sólo para la supervivencia global, y la localización, la edad y la ulceración para la supervivencia libre de enfermedad. Otras variables como el tipo histológico, el índice mitótico o el grado de invasión, a pesar de tener significación estadística en el estudio univariado, la perdieron en el estudio multivariado. CONCLUSIONES: El espesor tumoral es el factor pronóstico más importante para predecir la supervivencia en pacientes con melanoma localizado. Otros factores como el sexo, el infiltrado inflamatorio, la localización, la edad o la ulceración también tienen un papel relevante en el pronóstico

BACKGROUND AND OBJECTIVE: Several clinical and histological prognostic factors have been identified in localized melanoma. However, further studies with better defined and more reproducible histological parameters are needed. Our aim was to identify the prognostic factors for survival in cutaneous melanoma in the Spanish population. PATIENTS AND METHOD: Six hundred and thirty nine patients with localized melanoma, stages I and II of the last version of the American Joint Committee on Cancer staging system for cutaneous melanoma, with 2 years of follow-up or documented relapse, were selected from the data base of the Department of Dermatology. Univariate and multivariate Cox regression analyses were performed for overall and disease free survival. RESULTS: Tumor thickness appeared as the most important prognostic factor for both overall and disease free survival in the multivariate analysis. Inflammatory infiltrate and sex were only significant for overall survival, and location, age and ulceration were significant for disease free survival. Other variables, such as histological type, mitotic rate or level of invasion, lost their prognostic significance in the multivariate analysis. CONCLUSIONS: Tumor thickness is the most important prognostic factor to predict survival in localized melanoma. Other factors such as sex, inflammatory infiltrate, location, age or ulceration, have also an important role in prognosis

[Treatment of severe refractory psoriasis with infliximab]. / Tratamiento de la psoriasis extensa y refractaria con infliximab.

BACKGROUND AND OBJECTIVE: Infliximab is a chimeric monoclonal antibody that binds to tumor necrosis factor alpha and blocks the inflammatory response. The purpose of this study was to assess the effects of infliximab in patients with severe and refractory psoriasis. PATIENTS AND METHOD: Eleven patients with severe and refractory psoriasis were included in an open-label clinical trial. Patients received infliximab 5 mg/kg intravenously at weeks 0, 2, 6 and every 8 weeks. Psoriasis Assessment and Severity Index (PASI) and BSA (Body Surface Assessment) were used to monitor disease activity with each dose. Results at weeks 6 and 30 are shown. RESULTS: 90% of patients improved their PASI and BSA basal scores early at sixth week, achieving 63.6% (PASI75) and 72.7% (BSA50). This improvement was maintained until the 30th week (54.5% and 72.7%, respectively). Infliximab was well tolerated and there was no significant adverse reaction. CONCLUSIONS: Infliximab seems an effective therapy for severe and refractory psoriasis.